The mechanism of shape-dependent stochastic asymmetric cell division

细胞间的可变性作为生物系统的一个组成部分越来越受到重视。在这个项目中，我们探索了细胞形状的差异如何影响未来细胞行为的决定。在斑马鱼胚胎中，V2a和V2b两种V2中间神经元是由普通的V2祖细胞产生的。有人认为，V2前体细胞沿准随机方向分裂，在细胞分裂时不存在细胞命运偏差。然而，我们发现不同形状的V2祖细胞不仅与细胞分裂方向有关，而且以概率方式与二元细胞命运决定有关。我们还建立了形状依赖的随机V2细胞不对称分裂的抽象模型。我们在Silico中对该模型进行了数学模拟分析，并通过操纵斑马鱼胚胎进行了检验。我们的跨学科方法揭示了形状依赖的随机不对称细胞分裂的设计原理。

Cell-to-cell variability is increasingly appreciated as an integral part of biological systems. In this project, we explored how difference in cell shape affects the determination of future cell behavior. In zebrafish embryos, two kinds of V2 interneurons, V2a and V2b are generated from common V2 progenitor cells. It has been suggested that V2 progenitor cells divide along quasi-random directions and there is no cell fate bias at the time of cell division. However we found that varied shapes of V2 progenitor cells are coupled not only to the cell division orientation but also to the binary cell fate determination in a probabilistic manner. We also established an abstract model for shape-dependent stochastic V2 cells' asymmetric division. We analyzed this model by mathematical simulation in silico, and inspected it by manipulating the zebrafish embryos. Our interdisciplinary approach revealed the design principle for the shape-dependent stochastic asymmetric cell division.